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Focused on Glaucoma, Aerie Looks Toward Unblinding Critical Data

Xconomy New York — 

Glaucoma is a ripe opportunity for drug developers. Generics litter the field, yet it’s a roughly $5 billion market that will only grow with an aging population. What’s more, nothing out there cures the disease. Patients typically take eye drops, chronically, for the rest of their lives.

In other words, there’s room for innovation. That’s what led successful ophthalmology executive Vicente Anido Jr. to Bedminster, NJ-based Aerie Pharmaceuticals, one of the leading contenders with a new approach to the disorder.

By the end of the year, Aerie (NASDAQ: AERI) will report the results of three different Phase 3 trials for a drug called Rhopressa, an experimental glaucoma treatment. A late-stage study for a follow-up drug, Roclatan, should begin this year as well.

These trials will provide important information, like how well the drugs hold up over time, and how their side effects compare to other treatments. If successful, the trials could also signal that the standard of care for glaucoma, which has been stagnant for at least a decade, might be changing.

Competition is heating up in the glaucoma space, and for good reason: it’s a growing market. About 2.7 million people in the U.S. live with glaucoma, a figure expected to climb to 4.3 million by 2030, according to the National Eye Institute.

That market also happens to be dominated by a group of drugs, many of them generic, known as prostaglandin analogues (PGAs). Companies have crowded the field trying to one-up these PGAs in one way or another. Through its Bausch + Lomb subsidiary, for instance, Valeant Pharmaceuticals (NYSE: VRX) is expected to soon seek FDA approval of a drug that aims to make the most commonly prescribed PGA, known as latanoprost (Xalatan), more effective by adding a nitric oxide component. Bedford, MA-based Ocular Therapeutix (NASDAQ: OCUL) and Research Triangle Park, NC-based Envisia Therapeutics, among others, are developing ways to deliver PGAs into the eye over an extended period of time.

Others like Japan and Seattle-based Acucela and Inotek Pharmaceuticals (NASDAQ: ITEK) of Lexington, MA, are looking at different molecular targets for drugs that, at minimum, work in tandem with PGAs.

And then there’s Aerie, which is doing a little bit of everything. One drug (Rhopressa) is meant to be an adjunct therapy for PGAs or, in some cases, a replacement. The other drug (Roclatan), is meant to completely supplant PGAs and as Anido (pictured above) says, be a doctor’s “biggest gun” against glaucoma. Despite the competition, and the questions that Aerie still has to answer with data, experts are intrigued by its prospects.

“I think [Rhopressa] sounds really good,” says Richard Madonna, the chairman of clinical education, as well as a professor, at SUNY College of Optometry in New York, who isn’t involved with Aerie. “It’ll be very interesting if and when it does come to market.”

The reason: Aerie’s method is a return, of sorts, to the roots of glaucoma treatment. The first glaucoma drug was pilocarpine, or pilo, a drug derived from the jaborandi tree, a shrubby native of South and Central America and the West Indies.

Pilo directly solves a plumbing problem. That is, it relieves pressure that builds up when the trabecular meshwork (TM), a mesh-like filter that serves as the eye’s main fluid drainage system, gets clogged. When it does, aqueous humor, the gel-like fluid that shuttles nutrients through the eye, doesn’t drain properly. The excess fluid puts pressure on, and ultimately damages the optic nerve. If the pressure isn’t relieved, patients can gradually lose their vision.

While pilo relieves that pressure, it’s a very flawed drug and rarely used. It has to be taken four times a day, causes severe redness, and hampers peoples’ ability to focus.

Because of those faults, pilo gave way to so-called beta blockers like timolol, introduced in the late 70s, and later PGAs, once-a-day drops which arrived around the year 2000 and quickly became the standard of care for glaucoma.

Beta-blockers are now adjunctive therapies for people who don’t respond to PGAs (still a large market, as nearly half of U.S. glaucoma patients use a second therapy).

Like pilo, PGAs are no picnic. They irritate the eyes, causing redness; peoples’ eye color can change if they’ve got light-colored pupils; lashes can grow abnormally (Allergan turned this side-effect into a lash-growing drug called Latisse); fatty tissue around the eyes can dissipate.

While PGAs only impact a secondary drainage system, Rhopressa and Roclatan target the TM, the primary draining system, itself.

They do this by blocking two targets: rho kinase and norepinephrine transporter (NET). Blocking rho relaxes the cells in the TM, helping fluid pass through. Blocking NET slows fluid production. The drugs also reduce pressure in another ocular drain pipe, the episcleral vein. Roclatan has another added boost: it’s a combination of Rhopressa and latanoprost.

Aerie was spun out of the work of David Epstein and Eric Toone at Duke University in 2005 and raised $75 million in venture money from TPG Biotech, Alta Partners, and others.

Those VCs lured Anido to lead the company in July 2013. A year earlier, he’d sold another eye drug maker, Ista Pharmaceuticals, to Bausch + Lomb for $500 million. Aerie’s backers hoped his Wall Street cred would intrigue public investors, and the plan worked—Aerie went public just three months after Anido arrived, and raised around $70 million.

In October 2013, Aerie priced a tick lower than it hoped, at $10 per share instead of $12 to $14, but it’s been steadily climbing since. Shares closed at $28.93 apiece Monday, about three times its IPO price. Anido says most of Aerie’s backers have had “about five to six-times returns already, if not more.”

But Anido still must guide Aerie to the commercial finish line. That starts with Rhopressa. Anido says the first of the drug’s three phase 3 studies will read out in May, with the other two following later in the year. Then there’s Roclatan, which will enter late-stage testing later this year.

There are a few things to watch out for in the upcoming data. The first is durability. In early clinical trials, Rhopressa lowered eye pressure and kept it down for about a month. Anido says that skeptics “have tried to make a big deal” about the fact that Aerie’s previous rho kinase blocker wore off after a few weeks. Aerie no longer makes that version, but Rhopressa’s durability is being put to the test: All Phase 3 studies treat patients with Rhopressa for at least 90 days. In one of those studies, patients will be on drug for a year.

The data should also help determine where Rhopressa fits into current drug regimens. In previous trials, the drug hasn’t been as effective as PGAs for patients with high levels of eye pressure. But Rhopressa has bested PGAs in so-called “normal-tension” glaucoma patients, who have damaged optic nerves despite normal pressure levels. This is important, because a significant number of glaucoma patients are in this normal-tension group, Madonna says.

“I think it’s very important that you’d get more bang for your buck in patients who have normal pressure,” he says. “Maybe I would move [normal-tension patients] to Rhopressa first as opposed to latanoprost, or any of the PGAs.”

Anido says Aerie is targeting normal-tension patients, patients with light eyes who worry about their eye color changing from PGAs, and those who need other adjunctive therapies.

The side effects in Aerie’s upcoming data will also be crucial. The biggest concern so far is redness. Rhopressa causes redness in between 20 and 30 percent of patients, compared to 16 to 20 percent for PGAs, Anido says, although he adds in most cases the redness is mild and has only caused a few patients to drop out of Aerie’s studies.

Still, it’s worth watching, particularly with Roclatan, which uses two different mechanisms known to cause redness.

“That could be a major issue,” Madonna says. “[But Roclatan] to me sounds like a winner if the side effect profile is appropriate.”

It won’t be long before Aerie finds out.